DESCRIPTION: The Center for Structural Biology at the University of Michigan has established the first cryo-electron microscopy (cryo-EM) facility on campus with a focus on molecular EM of biological assemblies. The facility aims to serve the growing needs of the scientific community within and outside UMICH towards state-of-the-art visualization and structural characterization of macromolecular complexes. The cryo-EM suite, which already includes a 100kV, a 120 kV, and a 200 kV transmission electron microscope (TEM), will soon host a high-resolution 300 kV TEM. This expansion is based on the success of the first 5 years of the facility's operation (more than 20 high-impact publications) and the need to extend its imaging capabilities in terms of applications, quality of data, and throughput. The current computational platform dedicated to EM is very limited and represents a major bottleneck for image processing of data, especially for single particle EM projects requiring many thousands of images. Given that the output of cryo-EM data will increase several fold with the combined use of the 200 and the 300 kV TEMs, both equipped with new direct electron detectors and automated image acquisition algorithms, the present proposal requests the funds for the acquisition of a powerful compute cluster that includes 96 nodes with a total of 1152 CPU cores. This high-end cluster will facilitate the processing of large cryo-EM datasets, the implementation of computationally demanding image processing algorithms, as well as the parallel processing for multiple projects. Combined with our powerful TEM platform, the addition of this advanced computer system will enable the rapid and sophisticated cryo-EM image processing for many projects addressing the structure of important biological assemblies from intermediate to high resolution. The combination of these technologies will complement numerous NIH- funded projects of well-established biological programs within and outside UMICH. For the purpose of this application, we include a number of project descriptions that would greatly benefit from the acquisition of this instrument.